The natural history of D. pneumoniae infection will be studied in prospective fashion in 100 infants followed from birth through 2 years of age. Nasopharyngeal cultures will be obtained at regular intervals to detect carriage or subclinical infection. Bacteriologic methods include: cultivation of swabs or other culture material on selective blood agar medium, blood broth and mouse inoculation. D. pneumoniae are confirmed and serotyped by Neufeld reaction using Danish reference antisera. Episodic clinical illness observed to develop in patients in the prospective study will be carefully evaluated in relation to recovery of D. pneumoniae. Serial serum specimens, obtained at least quarterly, will be examined for antipneumococcal antibody by either radioimmunoassay, opsonization techniques, or both. Epidemiologic surveillance studies to determine prevalent pneumococcal serotypes among children presenting with upper respiratory tract infection will be conducted throughout the period of study. Isolates from well documented clinical syndromes (meningitis, septicemia and bacteremic pneumonia) from children and adults will be serotyped, relating predominant types to specific diesease syndromes and host-age range. Patients judged to have excessive numbers of pneumococcal infections will be further evaluated for host defense capability specifically to determine functional activity of serum capability for enhancement of phagacytosis and serum immunogloublins will be determined. The relation between recurrent infection by a given type, antibiotic therapy and evolution of specific antipneumococal antibody will also be determined. Data analysis is to be computer-assisted, using a combination of existing and projected programs. In the prospective study group, correlations between carriage, subclinical infection, and clinical infection, including recurrent illness and the development of specific antibody including serum opsonizing antibody, are the primary areas of emphasis.